scholarly journals Effects of mild and moderate renal dysfunction on pharmacokinetics, pharmacodynamics, and safety of dotinurad: a novel selective urate reabsorption inhibitor

2019 ◽  
Vol 24 (S1) ◽  
pp. 17-24 ◽  
Author(s):  
Hiroyuki Fukase ◽  
Daisuke Okui ◽  
Tomomitsu Sasaki ◽  
Masahiko Fushimi ◽  
Tetsuo Ohashi ◽  
...  
Keyword(s):  
Renal Function ◽  
Uric Acid ◽  
Renal Dysfunction ◽  
Serum Uric Acid ◽  
Normal Renal Function ◽  
Reduction Rate ◽  
Significant Difference ◽  
Function Group ◽  
Urate Reabsorption ◽  
Renal Function Group

Abstract Background Dotinurad, a novel selective urate reabsorption inhibitor, exerts a serum uric acid-lowering effect by selectively inhibiting urate transporter 1 (URAT1) in patients with hyperuricemia. It is generally known that the progression of renal dysfunction is associated with a reduction in the serum uric acid-lowering effects of uricosuric drugs. We, therefore, investigated the pharmacokinetics (PK), pharmacodynamics (PD), and safety of dotinurad in subjects with renal dysfunction. Methods This was a parallel-group, open-label, single-dose clinical pharmacology study. Dotinurad (1 mg) was administered once, orally to subjects with mild (estimated glomerular filtration rate [eGFR], ≥ 60 to < 90 mL/min/1.73 m2) or moderate (eGFR, ≥ 30 to < 60 mL/min/1.73 m2) renal dysfunction or normal (eGFR, ≥ 90 mL/min/1.73 m2) renal function. Results The time-course of mean plasma concentration of dotinurad had similar profiles across the groups. Regarding PK, there was no significant difference between the renal dysfunction groups and normal renal function group. Regarding PD, the maximum reduction rate in serum uric acid levels and the fractional uric acid excretion (FE) ratio (FE0–24/FE−24–0) were significantly lower in the moderate renal dysfunction group than in the normal renal function group. However, other PD parameters were not significantly different among the groups. No notable adverse events or adverse drug reactions were observed in this study. Conclusion These results suggested that no dose adjustment might be necessary when administering dotinurad to patients with mild-to-moderate renal dysfunction. ClinicalTrials.gov Identifier: NCT02347046.

scholarly journals Ischemic stroke, hemorrhage, and mortality in patients with non-valvular atrial fibrillation and renal dysfunction treated with rivaroxaban: sub-analysis of the EXPAND study

2021 ◽  
Author(s):  
Hirotsugu Atarashi ◽  
Shinichiro Uchiyama ◽  
Hiroshi Inoue ◽  
Takanari Kitazono ◽  
Takeshi Yamashita ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Renal Function ◽  
Renal Dysfunction ◽  
Normal Renal Function ◽  
Systemic Embolism ◽  
All Cause Mortality ◽  
Baseline Creatinine ◽  
Function Group ◽  
The Difference ◽  
Renal Function Group

AbstractThe EXPAND Study demonstrated the effectiveness and safety of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF) in routine clinical practice in Japan. This sub-analysis was conducted to reveal the effectiveness and safety of rivaroxaban in Japanese NVAF patients according to baseline creatinine clearance (CrCl) levels and rivaroxaban doses in the EXPAND Study. We examined 6806 patients whose baseline CrCl data were available and classified them into 2 groups: normal renal function group with CrCl ≥ 50 mL/min (n = 5326, 78%) and renal dysfunction group with CrCl < 50 mL/min (n = 1480, 22%). In the normal renal function group, 1609 (30%) received 10 mg/day (under-dose), while in the renal dysfunction group, 108 (7%) received 15 mg/day (over-dose). In the normal renal function group, under-dose of rivaroxaban was associated with higher all-cause mortality, while in the renal dysfunction group, over-dose was associated with higher incidence of major bleeding. In contrast, the incidence of stroke or systemic embolism was not different between the 2 groups regardless of the dose of rivaroxaban. In the propensity score matched analysis to adjust the difference in characteristics according to doses of rivaroxaban, the incidences of clinical outcomes were comparable between the 2 dose groups in both renal function groups. These results indicate that the dose of rivaroxaban should be reduced depending on the renal function, considering the balance between risks of bleeding and ischemia.

scholarly journals Comparative study of a novel selective urate reabsorption inhibitor “dotinurad” among patient groups with different stages of renal dysfunction

2021 ◽  
Author(s):  
Toshinari Takahashi ◽  
Takanobu Beppu ◽  
Yuji Hidaka ◽  
Tatsuo Hosoya
Keyword(s):  
Renal Function ◽  
Uric Acid ◽  
Renal Dysfunction ◽  
Serum Uric Acid ◽  
Uric Acid Level ◽  
Acid Level ◽  
Serum Uric Acid Level ◽  
Patient Groups ◽  
Urate Reabsorption

Abstract Background Dotinurad is a selective urate reabsorption inhibitor (SURI), which selectively inhibits URAT1 to lower serum uric acid levels in patients with hyperuricemia. Herein, the effects of dotinurad were compared among patient groups with different stages of renal dysfunction. Methods Patient data from four clinical trials were pooled and divided into four groups according to the stage of renal dysfunction to compare the effects of dotinurad at different stages. The grouping (stages G1–G3b) was based on the estimated glomerular filtration rate (eGFR) of the patients. In addition, patient data from a long-term study (34 or 58 weeks) were evaluated in the same manner. Results In the pooled analysis, the percentage of patients achieving a serum uric acid level of ≤ 6.0 mg/dL was 64.7–100.0% at a dose of 2 or 4 mg. In the long-term analysis, the percentage of patients achieving a serum uric acid level of ≤ 6.0 mg/dL was 60.0–100.0% at a dose of 2 or 4 mg. Although the outcomes in stage G3b were worse due to higher baseline serum uric acid levels, satisfactory outcomes were observed in all stages. Even in stages G3a and G3b, when renal function declined, the eGFR remained constant throughout the dose period. Conclusion The efficacy of dotinurad was confirmed in hyperuricemic patients with normal renal function (stage G1) and mild to moderate renal dysfunction (stage G2–G3b). Dotinurad was found to be effective in the treatment of hyperuricemia in patients with mild to moderate renal dysfunction.

scholarly journals Influence of renal function on clinico-pathological features of primary hyperparathyroidism

2003 ◽  
pp. 597-602 ◽  
Author(s):  
H Yamashita ◽  
S Noguchi ◽  
S Uchino ◽  
S Watanabe ◽  
T Murakami ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Insufficiency ◽  
Primary Hyperparathyroidism ◽  
Normal Renal Function ◽  
Urinary Calcium ◽  
Urinary Calcium Excretion ◽  
Calcium Excretion ◽  
Pathological Features ◽  
Function Group ◽  
Renal Function Group

OBJECTIVE: Disturbed renal function may play an important role in the clinico-pathological presentation of primary hyperparathyroidism (pHPT). We studied the influence of renal function on the clinico-pathological characteristics of 141 patients (123 women and 18 men) with surgically proven pHPT. METHODS: The 141 patients were assigned to one of two groups based on creatinine clearance (C(cr)) level: a renal insufficiency group (n=37) in which C(cr) of patients was <70 ml/min and a normal renal function group (n=104) in which C(cr) was > or =70 ml/min. Clinical presentation and biochemical indices were evaluated and compared between the two groups. RESULTS: Age, and frequency of hypertension and of diabetes mellitus were significantly (P<0.001, P<0.05 and P<0.05 respectively) higher in the renal insufficiency group than in the normal renal function group. Serum levels of calcium, intact parathyroid hormone and bone Gla protein were significantly (P<0.05) higher and the excised parathyroid weighed significantly more (P<0.05) in the renal insufficiency group than in the normal renal function group; however, serum 1,25-dihydroxyvitamin D (1,25(OH)(2)D) and 24 h urinary calcium excretion were significantly (P<0.001 and P<0.05 respectively) lower in the former than in the latter group. There was a significant inverse correlation between C(cr) level and serum calcium (r=0.315, P<0.001) and a significant positive correlation between C(cr) level, 1,25(OH)(2)D (r=0.315, P<0.001), and 24 h calcium excretion (r=0.458, P<0.0001). CONCLUSIONS: Clinico-pathological features of pHPT were notably influenced by even moderate renal insufficiency. Urinary calcium excretion decreased according to the decrease in glomerular filtration rate. Therefore, endocrinologists need to appraise urinary calcium excretion and renal function of pHPT patients when considering surgery or in discriminating familial hypocalciuric hypercalcemia.

scholarly journals Correlation of serum uric acid with renal function parameters in preeclampsia.

2020 ◽  
Vol 27 (12) ◽  
pp. 2703-2707
Author(s):  
Muddasir Zia ◽  
Rukhshan Khurshid ◽  
Uzma Jabbar ◽  
Adnan Riaz ◽  
Roohi Jabbar ◽  
...  
Keyword(s):  
Renal Function ◽  
Uric Acid ◽  
Serum Creatinine ◽  
Serum Uric Acid ◽  
Cross Sectional Study ◽  
Urinary Protein ◽  
Estimation Of Parameters ◽  
Cross Sectional ◽  
Significant Difference ◽  
Relationship Of

Objectives: Study was designed to find out the Correlation of serum uric acid with renal function parameters in Preeclampsia. Study Design: Cross Sectional study. Setting: Sir Ganga Ram Hospital Lahore. Period: July 2016 to July 2017. Material & Methods: Level of serum uric acid, serum creatinine and blood urea of 40 Preeclamptic women and 30 gestation-matched normotensive controls were estimated. Their Demographic and clinical characteristics were noted. The blood sample was analyzed for biochemical parameters, blood urea, serum uric acid, serum creatinine and urinary protein. Result: Mean age and gestational age of women was 25 weeks with BMI 29 Kg/m2. Level of serum uric acid and blood urea and serum creatinine were increased, but significant difference only observed with serum uric acid and blood urea with marked proteinuria. An inverse relationship of serum uric acid with urinary protein was observed. A direct relationship, of serum uric acid with serum creatinine was observed. Conclusion: it is concluded that estimation of parameters of renal function of preeclamptic women are important along with hyperuicaemia.

Serum uric acid levels are associated with lupus nephritis in patients with normal renal function

2018 ◽  
Vol 37 (5) ◽  
pp. 1223-1228 ◽  
Author(s):  
Ana Luisa Calich ◽  
Eduardo Ferreira Borba ◽  
Michelle Remião Ugolini-Lopes ◽  
Luiza Fuoco da Rocha ◽  
Eloisa Bonfá ◽  
...  
Keyword(s):  
Renal Function ◽  
Uric Acid ◽  
Lupus Nephritis ◽  
Serum Uric Acid ◽  
Normal Renal Function

Fosfomycin tromethamine for the Treatment of Cystitis in Abdominal Solid Organ Transplant Recipients With Renal Dysfunction

2017 ◽  
Vol 51 (9) ◽  
pp. 751-756 ◽  
Author(s):  
Luiza Kerstenetzky ◽  
Margaret R. Jorgenson ◽  
Jillian L. Descourouez ◽  
Glen Leverson ◽  
Warren E. Rose ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Dysfunction ◽  
Normal Renal Function ◽  
Treatment Success ◽  
Multivariable Analysis ◽  
Solid Organ Transplantation ◽  
Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Significant Difference

Background: Urinary tract infection (UTI) after abdominal solid organ transplantation (SOT) is associated with significant morbidity and mortality. Fosfomycin tromethamine (FOS), a uroselective antibiotic, is FDA approved for uncomplicated UTIs in women and is used off-label for complicated UTIs and prostatitis in men. Literature supporting the use of FOS in the SOT population is limited, and efficacy is questioned in the setting of renal dysfunction. Objective: To evaluate the success of FOS for the treatment of cystitis in SOT patients with renal dysfunction. Methods: This was a single-center, retrospective study using medical records. SOT recipients receiving at least 1 dose of FOS for treatment of cystitis between January 1, 2009, and April 30, 2015, were included. Treatment outcomes were analyzed with respect to renal function. Results: A total of 76 courses of FOS were identified in 64 patients. The renal dysfunction arm (creatinine clearance [CrCl] < 40 mL/min) included 33 patients with 39 FOS courses; the normal renal function arm (CrCl ≥ 40 mL/min) included 31 patients with 37 FOS courses. Mean CrCl was 23.3 ± 9.7 mL/min for the renal-dysfunction group and 65 ± 29.3 mL/min for the normal renal function group ( P < 0.01). No significant difference in treatment success was noted between CrCl <40 mL/min and CrCl ≥40 mL/min (31 [80%] vs 34 [92%], P = 0.12) in a unilateral analysis. After adjusting for confounders in a multivariable analysis, there was no difference in the risk of failure between CrCl <40 mL/min and CrCl ≥40 mL/min groups ( P = 0.70). Conclusion: FOS appears to be successful for the treatment of cystitis in SOT recipients in the setting of renal dysfunction.

scholarly journals The Prognostic Value of Serum Uric Acid in Hospitalized Patients with Acute Cerebral Infarction

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Bangjian Liu ◽  
Yongchao Pan ◽  
Li Cao ◽  
Jiajun Yang
Keyword(s):  
Renal Function ◽  
Uric Acid ◽  
Hospital Mortality ◽  
Prognostic Value ◽  
Multivariate Analyses ◽  
Acid Group ◽  
Hospitalized Patients ◽  
Function Group ◽  
Renal Function Group ◽  
Abnormal Renal Function

Background. Previous studies reported that the level of serum uric acid (SUA) was an important risk factor for acute cerebral infarction (ACI). However, the prognostic value of SUA levels in hospitalized patients with ACI has not been fully elucidated. The aim of this study was to investigate whether the SUA level on admission was associated with subsequent mortality in hospitalized patients with ACI. Methods. The clinical data of ACI patients obtained from December 2017 to December 2019 were retrospectively reviewed. χ 2 and Kaplan–Meier methods were used to compare the clinical differences and overall survival between patients with or without hyperuricemia, respectively. Univariate and multivariate analyses were used to identify independent prognoses. Results. In the total population, the in-hospital mortality of the hyperuricemia group was significantly higher than that of the normal uric acid group ( P = 0.006 ). In the abnormal renal function group, the in-hospital mortality among the hyperuricemia group was significantly higher than the normal uric acid group ( P = 0.002 ). However, there was no statistical difference of in-hospital mortality between the two groups in the normal renal function group ( P = 0.321 ). Univariate and multivariate analyses showed that a previous history of diabetes ( P = 0.018 ), hyperuricemia ( P = 0.001 ), and National Institutes of Health Stroke Scale (NIHSS) score on admission ( P ≤ 0.001 ) were independent factors for all samples. The hyperuricemia ( P = 0.003 ) on admission were independent factors for patients with abnormal renal function. Conclusions. In ACI patients with abnormal renal function, hyperuricemia may be associated with higher in-hospital mortality than patients with normal uric acid, and hyperuricemia may be an independent associated factor for in-hospital death in the subgroup patients.

scholarly journals Increased Short-Term and Mid-Term Major Complications Were Observed in Elderly Patients with Renal Dysfunction after Surgical Ventricular Restoration

2018 ◽  
Vol 21 (3) ◽  
pp. 194
Author(s):  
Fei Xu ◽  
Yangwu Song ◽  
Wei Feng ◽  
Xuan Li ◽  
Junzhe Du
Keyword(s):  
Renal Function ◽  
Elderly Patients ◽  
Renal Dysfunction ◽  
Normal Renal Function ◽  
P Value ◽  
Short Term ◽  
Surgical Ventricular Restoration ◽  
Function Group ◽  
The Impact ◽  
Ventricular Restoration

Background: This study was conducted to explore the impact of renal dysfunction on short-term and mid-term outcomes in elderly patients.Methods: Patients over 65 years of age receiving surgical ventricular restoration (SVR) were included in the study. They were stratified through estimated glomerular filtration rate (eGFR), with a cutoff point of 60 mL/min/1.73m2. Risk-adjusted analysis, including propensity score matching, was carried out to compare short-term and mid-term outcomes between the two groups of patients.Results: From January 1999 to December 2015, a total of 280 elderly patients underwent SVR. Of the patients, 79 had eGFR lower than 60 mL/min/1.73m2 and were considered to have renal dysfunction. Mortality was higher in the renal dysfunction group than the normal renal function group, with marginal significance (adjusted P value = .06). The need for mechanical supports (adjusted P value = .04) was higher in the renal dysfunction group. Hemofiltration (adjusted P value < .01) and requirements for transfusion (adjusted P value = .03) were significantly higher in the renal dysfunction group than in the group with normal renal function. The presence of renal dysfunction was associated with higher risk of major adverse cerebro-cardiovascular events (MACCE) than normal renal function (HR = 2.34, 95% CI = 1.34 - 4.08, P = .003).Conclusion: Compared to patients with normal renal function, elderly SVR patients with renal failure have a higher incidence of short-term mechanical support, mid-term mortality, and MACCE events.

scholarly journals Effects of Chicory on Serum Uric Acid, Renal Function, and GLUT9 Expression in Hyperuricaemic Rats with Renal Injury and In Vitro Verification with Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Yong-Nan Jin ◽  
Zhi-Jian Lin ◽  
Bing Zhang ◽  
Yun-Fei Bai
Keyword(s):  
Renal Function ◽  
Uric Acid ◽  
Renal Dysfunction ◽  
Serum Uric Acid ◽  
Renal Injury ◽  
Interstitial Fibrosis ◽  
Serum Uric Acid Level ◽  
In Vivo Studies ◽  
Renal Tubules

Hyperuricaemia (HUA) is an independent risk factor for chronic kidney disease. Urate crystals are deposited in the kidney and can cause renal tubular interstitial fibrosis, leading to renal dysfunction. Chicory extract (hereafter referred to as chicory) clearly reduced serum uric acid levels in rats with HUA induced by 10% fructose. This is the first study to observe the effect of chicory on serum uric acid levels and renal function in rats with HUA and renal injury. In vivo studies using hyperuricaemic rats with renal injury induced by yeast and adenine demonstrated that chicory decreased serum uric acid level, and its effect of delaying the progression of kidney injury was better than that of benzbromarone. In vitro cell experiments showed that this effect is related to the inhibition of GLUT9 protein expression in renal tubules and that lowering blood uric acid concentrations is one of the factors that alleviates renal damage. The results of this study indicate that chicory can be used as an alternative for alleviating renal dysfunction in hyperuricaemia.

scholarly journals Hyperuricemia is associated with progression of CKD: uric acid aggravates renal function

2019 ◽  
Author(s):  
Shulei Fan ◽  
Yang Zou ◽  
Amanda Y Wang ◽  
Mingjie Xu ◽  
Guisen Li ◽  
...  
Keyword(s):  
Renal Function ◽  
Uric Acid ◽  
Risk Factor ◽  
Serum Uric Acid ◽  
Metabolic Diseases ◽  
Cox Regression ◽  
Living Standard ◽  
Cox Regression Analysis ◽  
Significant Difference ◽  
The Mean

Abstract Background: With the change of living standard and dietary structure, the incidence of hyperuricemia is on the rise. Hyperuricemia has become one of the metabolic diseases threatening human health. There is paucity of literature on the association between serum uric acid levels and the progression of CKD. This study aimed at assessing the effect of serum baseline uric acid level on the progression of CKD. Methods: This retrospective study included 800 CKD patients in our center. The information on baseline and follow-up characteristics were collected from our Renal Treatment System (RTS) database. Cox regression analysis was used to evaluate the risk factors for CKD progression. The Kaplan–Meier analysis was used to test associations between serum uric acid levels and renal survival rates. Results: A total of 800 patients were included in the study, and the mean age at entry was 36.6±14.4 years. There was no significant difference in gender distribution. The mean eGFR, Cr, serum uric acid at baseline were 99.23±31.54 ml/min/1.73㎡, 82.08±41.40 μmol/L, 371.60±103.18 μmol/L, respectively. 306 (38.3%) patients had HUA and 494 (61.7%) had non-HUA. We established different adjusted models and found that HUA was a risk factor for CKD patients to reach the composite endpoint after adjustment in six models. All models show that HUA was a risk factor for the progression of CKD. Among them, model 4 (adjusted for Cr + Alb + age + BP + gender) was the best model with the largest HR value (HR:2.010, 95%CI:1.310-3.084, P<0.05). The cumulative survival rate of non-hyperuricemia group was higher than that of hyperuricemia group (P<0.001). Conclusions: Hyperuricemia was not only widespread in patients with CKD, but also a risk factor for the progression of CKD. Anti-hyperuricemia therapy may need to be considered in CKD patients to slow the disease progression, which needs to be tested further in clinical studies. Key words: hyperuricemia, chronic kidney disease, renal function, progression

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